Retinal neovascularization (RNV) represents the leading cause of blindness in humans and can be triggered by a variety of ocular insults, e.g., high glucose, radiation, and chemotherapy. RNV may be caused by REC death due to an exuberant pro-inflammatory response triggered by damages to the posterior vascularized portion of the eye (Brown et al., 1982; Viebahn et al., 1991; Zamber and Kinyoun, 1992). Because new vessels formed under hypoxia are fragile and leaky, RNV often leads to macular edema, retinal detachment and blindness. For example, as shown in FIG. 1, irradiation of the eye can trigger leukocyte adhesion, accumulation, and blockage of retinal vasculature, which may result in hypoxia, abnormal retinal neovascularization and ultimately loss of vision.
Treatments for RNV include glucocorticoids, anti-vascular endothelial growth factor (VEGF) monoclonal antibodies, and surgical intervention (panretinal photocoagulation [PRP]) (Aiello et al., 1995; Googe et al., 2011). These treatments are often not effective and also limited by side effects such as ocular hypertension, glaucoma, cataracts, retinal detachment, and endophthalmitis (Conti and Kertes, 2006; Gillies et al., 2006; Waisbourd et al., 2011).
We have discovered a new class of quinic acid analogs (QAAs) that are are resistant to bacterial degradation (Zeng et al., 2011; Zeng et al., 2009). We have previously demonstrated that the QAAs, e.g., KZ-41 (1,3,4,5-tetrahydroxy-1-cyclohexanecarboxylic acid), can exert a significant pro-survival effect in a whole murine model of high dose radiation injury. See U.S. Patent Application Publication No. 2012/0283331. Here we disclose another surprising discovery that QAAs can regulate REC viability due to radiation, chemotherapy or high glucose, and therefore prevent, treat or cure RNV-caused blindness.